It is proposed to study cellular interactions and humoral factors as they relate to hematopoietic differentiation. The areas to be studied include: (1) Studies of humoral and cellular interactions in deliberately-induced marrow failure in cats. Feline leukemia virus-infected animals will be studied serially to explore the evolution of marrow failure and leukemia in this model. (2) Attempted purification of growth factors from murine sources, specific for certain types of hematopoietic progenitors, will be carried out. If separation of factor activities is successful, the factor will be applied to long-term marrow culture systems in an attempt to influence early differentiation events. (3) Studies of myeloproliferative disorders in man will be designed to assess the rate of early myeloid and erythroid differentiation in abnormal clones as well as residual normal clones, and to determine the role of erythropoietin in man in regulating the population size of erythroid colony-forming units. The long-term goals are to understand the nature of early hematopoietic regulation in an experimental model of neoplasia and compare and contrast this information with studies in human myeloproliferative disorders.